Seroatlas · Human Serome Atlas

SLC4A1

Band 3 anion transport protein

Also known as: AE1, B3AT_HUMAN, CD233, DI, EPB3, FR, RTA1A, SW, WD, WR

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P02730
Gene: SLC4A1
Ensembl: ENSG00000004939
Chromosome: 17
Canonical length: 911 aa
Protein class: Blood group antigen proteins, CD markers, Disease related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted membrane proteins, Transporters

OverviewNCBI Gene

The protein encoded by this gene is part of the anion exchanger (AE) family and is expressed in the erythrocyte plasma membrane, where it functions as a chloride/bicarbonate exchanger involved in carbon dioxide transport from tissues to lungs. The protein comprises two domains that are structurally and functionally distinct. The N-terminal 40kDa domain is located in the cytoplasm and acts as an attachment site for the red cell skeleton by binding ankyrin. The glycosylated C-terminal membrane-associated domain contains 12-14 membrane spanning segments and carries out the stilbene disulphonate-sensitive exchange transport of anions. The cytoplasmic tail at the extreme C-terminus of the membrane domain binds carbonic anhydrase II. The encoded protein associates with the red cell membrane protein glycophorin A and this association promotes the correct folding and translocation of the exchanger. This protein is predominantly dimeric but forms tetramers in the presence of ankyrin. Many mutations in this gene are known in man, and these mutations can lead to two types of disease: destabilization of red cell membrane leading to hereditary spherocytosis, and defective kidney acid secretion leading to distal renal tubular acidosis. Other mutations that do not give rise to disease result in novel blood group antigens, which form the Diego blood group system. Southeast Asian ovalocytosis (SAO, Melanesian ovalocytosis) results from the heterozygous presence of a deletion in the encoded protein and is common in areas where Plasmodium falciparum malaria is endemic. One null mutation in this gene is known, resulting in very severe anemia and nephrocalcinosis. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

911 residues, UniProt reviewed canonical sequence.

>P02730|SLC4A1
     1  MEELQDDYED MMEENLEQEE YEDPDIPESQ MEEPAAHDTE ATATDYHTTS HPGTHKVYVE
    61  LQELVMDEKN QELRWMEAAR WVQLEENLGE NGAWGRPHLS HLTFWSLLEL RRVFTKGTVL
   121  LDLQETSLAG VANQLLDRFI FEDQIRPQDR EELLRALLLK HSHAGELEAL GGVKPAVLTR
   181  SGDPSQPLLP QHSSLETQLF CEQGDGGTEG HSPSGILEKI PPDSEATLVL VGRADFLEQP
   241  VLGFVRLQEA AELEAVELPV PIRFLFVLLG PEAPHIDYTQ LGRAAATLMS ERVFRIDAYM
   301  AQSRGELLHS LEGFLDCSLV LPPTDAPSEQ ALLSLVPVQR ELLRRRYQSS PAKPDSSFYK
   361  GLDLNGGPDD PLQQTGQLFG GLVRDIRRRY PYYLSDITDA FSPQVLAAVI FIYFAALSPA
   421  ITFGGLLGEK TRNQMGVSEL LISTAVQGIL FALLGAQPLL VVGFSGPLLV FEEAFFSFCE
   481  TNGLEYIVGR VWIGFWLILL VVLVVAFEGS FLVRFISRYT QEIFSFLISL IFIYETFSKL
   541  IKIFQDHPLQ KTYNYNVLMV PKPQGPLPNT ALLSLVLMAG TFFFAMMLRK FKNSSYFPGK
   601  LRRVIGDFGV PISILIMVLV DFFIQDTYTQ KLSVPDGFKV SNSSARGWVI HPLGLRSEFP
   661  IWMMFASALP ALLVFILIFL ESQITTLIVS KPERKMVKGS GFHLDLLLVV GMGGVAALFG
   721  MPWLSATTVR SVTHANALTV MGKASTPGAA AQIQEVKEQR ISGLLVAVLV GLSILMEPIL
   781  SRIPLAVLFG IFLYMGVTSL SGIQLFDRIL LLFKPPKYHP DVPYVKRVKT WRMHLFTGIQ
   841  IICLAVLWVV KSTPASLALP FVLILTVPLR RVLLPLIFRN VELQCLDADD AKATFDEEEG
   901  RDEYDEVAMP V

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SLC4A1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 10
Mean surface accessibility (rSASA): 0.28
Highest tissue expression: 380 nTPM

Expression across tissuesHPA

Tissue

bone marrow: 380 nTPM
kidney: 39 nTPM
placenta: 10 nTPM
spleen: 8.8 nTPM
liver: 1.5 nTPM
tongue: 1.4 nTPM

Single-cell type

erythrocytes: 670 nCPM
erythrocyte progenitors: 365 nCPM
renal collecting duct intercalated cells: 310 nCPM
renal connecting tubule cells: 12 nCPM
epididymal basal cells: 9.3 nCPM
epididymal clear cells: 8.2 nCPM

Immune cell

basophil: 0.7 nTPM
neutrophil: 0.6 nTPM
NK-cell: 0.2 nTPM
total PBMC: 0.2 nTPM
eosinophil: 0.1 nTPM
memory B-cell: 0.1 nTPM

Brain region

cerebral cortex: 2.4 nTPM
cerebellum: 2.1 nTPM
choroid plexus: 1.7 nTPM
medulla oblongata: 1.7 nTPM
thalamus: 1.7 nTPM
pons: 1.6 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SLC4A1.

Disease | AllUniProt

Conditions SLC4A1 is implicated in, by any mechanism.

Ovalocytosis, Southeast Asian (SAO) MIM:166900
Spherocytosis 4 (SPH4) MIM:612653
Renal tubular acidosis, distal, 1 (DRTA1) MIM:179800
Renal tubular acidosis, distal, 4, with hemolytic anemia (DRTA4) MIM:611590
Cryohydrocytosis (CHC) MIM:185020

Disease | GeneticClinVar

234 pathogenic / likely-pathogenic of 1,014 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Hereditary spherocytosis type 4
Autosomal dominant distal renal tubular acidosis
11 conditions
SLC4A1-related disorder
Renal tubular acidosis, distal, 4, with hemolytic anemia

Disease | ImmuneIEDB

Conditions an epitope on SLC4A1 was assayed in.

systemic lupus erythematosus B cell
rheumatoid arthritis B cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.35
gnomAD pLI: 0.85
gnomAD missense Z: 1.66
DepMap mean gene effect: -0.09
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SLC4A1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SLC4A1 as an antibody target. Whether an autoantibody or antibody against SLC4A1 could matter depends on whether native SLC4A1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SLC4A1 is annotated at the cell surface, where native SLC4A1 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label SLC4A1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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